rs517761

Variant names:

• chr7-103728571-T-C
• rs517761
• NM_005045.4:c.657-364A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-103728571-T-C
• chr7-103728571-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005045.4(RELN):​c.657-364A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,974 control chromosomes in the GnomAD database, including 29,747 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.61 (29747 hom., cov: 31)
• Consequence: RELN NM_005045.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 2 publications found

Genes affected

RELN (HGNC:9957): (reelin) This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

RELN Gene-Disease associations (from GenCC):

• lissencephaly with cerebellar hypoplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Norman-Roberts syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P, PanelApp Australia
• familial temporal lobe epilepsy 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• autosomal dominant epilepsy with auditory features

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ankylosing spondylitis

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• complex neurodevelopmental disorder

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RELN	NM_005045.4	c.657-364A>G		intron_variant	Intron 6 of 64	ENST00000428762.6	NP_005036.2
RELN	NM_173054.3	c.657-364A>G		intron_variant	Intron 6 of 63		NP_774959.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RELN	ENST00000428762.6	c.657-364A>G		intron_variant	Intron 6 of 64	5	NM_005045.4	ENSP00000392423.1

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92642 AN: 151854 Hom.: 29692 Cov.: 31

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.492

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.530

Gnomad OTH AF: 0.610

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.610 AC: 92750 AN: 151974 Hom.: 29747 Cov.: 31 AF XY: 0.606 AC XY: 45026 AN XY: 74254

African (AFR) AF: 0.823 AC: 34141 AN: 41502

American (AMR) AF: 0.515 AC: 7850 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 1705 AN: 3468

East Asian (EAS) AF: 0.631 AC: 3258 AN: 5164

South Asian (SAS) AF: 0.574 AC: 2756 AN: 4804

European-Finnish (FIN) AF: 0.492 AC: 5178 AN: 10530

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.530 AC: 35984 AN: 67956

Other (OTH) AF: 0.608 AC: 1279 AN: 2102

Alfa AF: 0.550 Hom.: 25564

Bravo AF: 0.625

Asia WGS AF: 0.562 AC: 1952 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.50
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs517761; hg19: chr7-103369018;